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Huangqin Tang (HQT), a traditional Chinese medicine formula, is commonly used in clinical practice for the treatment of inflammatory bowel diseases. It has been reported that HQT exerts antitumor effects on colitis-associated colorectal cancer (CAC). However, the mechanism by which HQT interferes with the inflammation-to-cancer transformation remains unclear. The purpose of this study was to dynamically evaluate the efficacy of HQT in alleviating or delaying CAC and to reveal the underlying mechanism. We established a mouse model of CAC using azoxymethane combined with 1.5% dextran sodium sulphate. The efficacy of HQT was evaluated based on pathological sections and serum biochemical indices. Subsequently, amino acids (AAs) metabolism analyses were performed using ultra-performance liquid chromatography-tandem mass spectrometry, and the phosphatidylinositol 3 kinase/protein kinase B/mechanistic target of rapamycin (PI3K/AKT/mTOR) pathway was detected by western blotting. The data demonstrated that HQT could alleviate the development of CAC in the animal model. HQT effectively reduced the inflammatory response, particularly interleukin-6 (IL-6), in the inflammation induction stage, as well as in the stages of proliferation initiation and tumorigenesis. During the proliferation initiation and tumorigenesis stages, immunohistochemistry staining showed that the expression of the proliferation marker Ki67 was reduced, while apoptosis was increased in the HQT group. Accordingly, HQT substantially decreased the levels of specific AAs in the colon with CAC, including glutamic acid, glutamine, arginine, and isoleucine. Furthermore, HQT significantly inhibited the activated PI3K/AKT/mTOR pathway, which may contribute to suppression of cell proliferation and enhancement of apoptosis. HQT is effective in alleviating and delaying the colon "inflammation-to-cancer". The mechanism of action may involve HQT maintained AAs metabolism homeostasis and regulated PI3K/AKT/mTOR pathway, so as to maintain the balance between proliferation and apoptosis, and then interfere in the occurrence and development of CAC. [Display omitted] [ABSTRACT FROM AUTHOR]

Many studies have shown that the imbalance of the intestinal flora and metabolite can lead to the development of ulcerative colitis (UC), but their role in recurrent-UC is still unclear. We studied the intestinal flora and metabolites associated with recurrent-UC to elucidate the mechanism and biomarkers of recurrent-UC. Ulcerative colitis (UC) models in active, remission, and recurrence stages were established, and the abundance of intestinal flora was determined by 16 S rRNA sequencing. The changes in the metabolites present in feces and serum were analyzed by UPLC-MS/MS. We identified 24 metabolites in feces and serum, which might be used as diagnostic and predictive biomarkers of recurrent-UC. The dominant flora of recurrent-UC included Romboutsia , UCG-005, etc. The results of a network analysis found that long-chain fatty acids and phenylalanine were strongly correlated with Firmicutes and Proteobacteria, which indicated that the recurrence of UC might be closely related to metabolites and microorganisms. The changes in intestinal microbiota and metabolites are closely related to the development of UC. Microbiota is an important inducer of UC, which can regulate metabolites through the 'microorganism-gut-metabolite' axis. It may provide a new method for the prediction and treatment of UC. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease closely related to gut microbiota dysbiosis and intestinal homeostasis imbalance. Sishen Pill&Tongxieyaofang (SSP-TXYF) has a long history of application in traditional Chinese medicine and is widely used in UC clinics. However, its mechanism of action is still unclear., Purpose: This study aimed to explore the potential regulatory role of SSP-TXYF in protecting against UC through metabolites produced by the intestinal microbiota, and elucidate its underlying molecular mechanism., Study Design and Methods: 16S rRNA and UPLC-QE-Orbitrap-MS were used to assess the microbiota and short-chain fatty acids (SCFAs). A rat model of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced gut microbiota dysbiosis was used to study the effects of SSP-TXYF on UC in vivo. Intestinal epithelial cells-6 (IEC-6) were treated with lipopolysaccharide (LPS). The intestinal mucosal barrier (IMB) functions were investigated by alcian blue staining and western blot analysis. The mechanism of SSP-TXYF influenced the HIF-1α acetylation pathway was examined by real-time fluorescence quantitative PCR (qPCR), Western blotting, and Co-immunoprecipitation., Results: Using 16S rRNA gene-based microbiota analysis, we found that SSP-TXYF ameliorated TNBS-induced gut microbiota dysbiosis. We found that SSP-TXYF significantly inhibited the decreased abundance of Firmicutes in UC rats, in addition, the abundance of Actinobacteria was also improved. The mechanism of SSP-TXYF-treated TNBS-induced UC resulted from improved IMB functions via the activation of hypoxia-inducible factor-1 (HIF-1α) acetylation. Notably, SSP-TXYF Enriched microbiota-derived metabolites propionate and butyrate, which could activate HIF-1α acetylation in IEC. Furthermore, exogenous treatment of propionate and butyrate reproduced similar protective effects as SSP-TXYF to UC through improving HIF-1α-dependent IMB functions., Conclusions: Overall, our findings suggest that the gut microbiota-propionate/butyrate-HIF-1α-IMB axis plays an important role in SSP-TXYF-maintaining intestinal homeostasis, which may represent a novel approach for UC prevention via the intervention of any link in this axis., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background: Enhancing white adipose tissue (WAT) browning combats obesity. The RIIβ subunit of cAMP-dependent protein kinase (PKA) is primarily expressed in the brain and adipose tissue. Deletion of the hypothalamic RIIβ gene centrally induces WAT browning, yet the peripheral mechanisms mediating this process remain unexplored. Methods: This study investigates the mechanisms underlying WAT browning in RIIβ-KO mice. Genetic approaches such as β3-adrenergic receptors (β3ARs) deletion and sympathetic denervation of WAT were utilized. Genome-wide transcriptomic sequencing and bioinformatic analysis were employed to identify potential mediators of WAT browning. siRNA assays were employed to knock down mTOR and lipin1 in vitro , while AAV-shRNAs were used for the same purpose in vivo . Results: We found that WAT browning substantially contributes to the lean and obesity-resistant phenotypes of RIIβ-KO mice. The WAT browning can be dampened by β 3 ARs deletion or WAT sympathetic denervation. We identified that adipocytic mTOR and lipin1 may act as mediators of the WAT browning. Inhibition of mTOR or lipin1 abrogates WAT browning and hinders the lean phenotype of RIIβ-KO mice. In human subcutaneous white adipocytes and mouse white adipocytes, β 3 AR stimulation can activate mTOR and causes lipin1 nuclear translocation; knockdown of mTOR and Lipin1 mitigates WAT browning-associated gene expression, impedes mitochondrial activity. Moreover, mTOR knockdown reduces lipin1 level and nuclear translocation, indicating that lipin1 may act downstream of mTOR. Additionally, in vivo knockdown of mTOR and Lipin1 diminished WAT browning and increased adiposity. Conclusions: The β 3 AR-activated mTOR-lipin1 axis mediates WAT browning, offering new insights into the molecular basis of PKA-regulated WAT browning. These findings provide potential adipose target candidates for the development of drugs to treat obesity., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)